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Coronavirus vaccines: the top 10 of the most advanced

2020-07-14T16:38:50.527Z


There are 160 experimental candidates, of which 23 are already tested in humans.07/13/2020 - 15:22 Clarín.com Good Life The coronavirus pandemic changed our lives, perhaps forever. We have more than half a million deaths and almost 13 million cases worldwide, according to updated data from the Johns Hopkins Center for Science and Systems Engineering, with a number of cases and deaths that does not stop growing in countries like the United States. United and Brazil. Vaccine ...


07/13/2020 - 15:22

  • Clarín.com
  • Good Life

The coronavirus pandemic changed our lives, perhaps forever. We have more than half a million deaths and almost 13 million cases worldwide, according to updated data from the Johns Hopkins Center for Science and Systems Engineering, with a number of cases and deaths that does not stop growing in countries like the United States. United and Brazil.

Vaccine development often takes years of research and testing before reaching the clinical phase, but this crisis accelerated the entire process . Companies and research centers around the world are working at a frantic pace to have a safe and effective vaccine next year that protects us against the effects of SARS-CoV-2.

The Donald Trump Administration, which launched its controversial Operation Warp Speed ​​in May, also contributed to this hectic speed. This program has selected, so far, five vaccine projects that will receive billions of dollars in federal funding before there is evidence that they really work, including Oxford University and AstraZeneca and the American biotech project. Modern, as reported by The New York Times.

Mercedes Jiménez, biochemist at the Margarita Salas Biological Research Center (CIB-CSIC) prefers not to "comment" on US policy in competition for the vaccine and highlights the "great scientific work that is being carried out to obtain it."

According to the scientific news agency SINC, "a lot of investigative effort is being invested to obtain an effective prophylaxis against COVID-19 and I think it will bear many fruits. The researcher considers that the various approaches that are being used for the development of the vaccine "will make the effectiveness different." In fact, he believes, in this race "it will take more than one winning horse . "

At this point, the CIB-CSIC immunologist María Montoya also agrees, indicating that “the scientific community is contributing all the knowledge possible to obtain the desired vaccine. All the strategies are being investigated and tested : vaccines with replicative and non-replicative vectors, RNA, DNA, subunit protein, inactivated virus and recombinant viral pseudoparticles, ”he points out.

Montoya believes that "of all the candidates, we will have several vaccines that will generate immunity, perhaps partial or perhaps total. But any vaccine, even if it gives partial protection, will be better than not having any. ”

For his part, Jorge Carrillo, a researcher in immunobiology at IrsiCaixa, recalls that in this race the groups involved are also risking their prestige and future. "I don't think," he tells SINC, "that any of them is going to get a candidate with less than 60% efficacy" [the minimum level of protection required so far by drug agencies]. Carrillo points out that "it would not be profitable because it would be a very short-lived vaccine that could be immediately replaced by another that achieves higher levels of protection."

In the competition, Montoya says that “those that are more advanced, because they are less complex, are those that have taken a part of the SARS-CoV-2 or a subunit, and have been inserted into a vector. In these vaccine prototypes, "the immune system 'only' sees a part of the virus and it could happen that they confer partial immunity." Still, "they would be very useful to vaccinate the population," he insists. "Those that contain more parts of the virus are more complicated to produce and therefore will come later."

Currently, there are 160 experimental vaccines against Covid-19. Of these, 23 are already being tested in one or more of the three phases of human trials, according to the latest data from the World Health Organization (WHO). Here we have selected those that are in the most advanced stages.

1. Oxford University / AstraZeneca

United Kingdom, phase III trials

The first in this classification is the one developed by the University of Oxford and AstraZeneca. It has already entered phase III of efficacy tests, it is being tested with 4,000 volunteers in the United Kingdom, it will shortly be tested in Brazil with 5,000 people and in South Africa with 2,000. Trials include children 5 to 12 years old and adults over 70 years.

The prototype is called ChAdOx1 nCoV-19 and is made from a virus called ChAdOx1, a weakened version of a common cold virus (adenovirus), which causes infections in chimpanzees and has been genetically engineered so that it is impossible for it to replicate in humans.

The candidate was redesigned to contain protein S (from English spike), present in the coronavirus, which gives it its characteristic tip and crown appearance on the surface. The researchers hope that the vaccine, by introducing this protein to our immune cells, can induce the production of specific antibodies.

The pharmaceutical company AstraZeneca, a partner of the British university in this project, has an agreement with the United States Government to start a trial with 30,000 people in that country and received funding from the US Administration under the Operation Warp Speed ​​program.

About this project, Montoya believes that this subunit vaccine “is interesting because it uses a vector that has already given very good results in vaccinations against other diseases, such as MERS, influenza, tuberculosis, the Chikungunya virus and Zika. Now, we need to know what type of immunity it induces against COVID-19 ”, he clarifies.

AstraZeneca signed with partners in the United Kingdom and the United States for the mass production of the vaccine, so that it can be distributed if conclusive evidence of efficacy and safety is finally achieved. The firm assured that its total manufacturing capacity is 2 billion doses, according to the STAT medical news website.

The CEO of the firm, Pascal Soriot, declared a few weeks ago that “the vaccine could protect for a period of one year , after which it would be necessary to re-vaccinate. I also point out that the first emergency vaccines may be available in October. "

Since the genetic sequence of the virus was shared, researchers around the world have started developing candidate vaccines. (Douglas MAGNO / AFP)

2. Modern

United States, phase III trials

Another of the most advanced projects is that of the modern American firm. Its candidate, mRNA-1273, entered Phase III testing and the company plans to test it with 30,000 volunteers in July .

However, the firm's shares fell 7% last Thursday, after STAT reported a delay in this great trial , due to changes that Moderna wants to introduce in its study plan. The company still believes it will be able to start testing this month, according to these sources.

The vaccine from this biotech, based in Cambridge, Massachusetts, is based on the use of messenger RNA (mRNA) technology. Once injected into the body, it sends the message to the cells to make virus-like proteins that are activated and function as antibodies.

Mercedes Jiménez believes that "this vaccine based on genetic material is a pioneer in its use in humans, it will require the development of safe technologies for its transport within the body." Therefore, "it is a significant challenge and it will be very interesting to see the type of immune response it can provide," he stresses.

3. CanSino Biologics China

Trials in thousands of military

The CanSino Biologics experimental vaccine, developed in collaboration with the Chinese Academy of Military Sciences, made headlines a couple of weeks ago when this biotech announced that its candidate Ad5-nCoV had received authorization from the Central Military Commission to use its candidate among members of the armed forces without completing clinical trials.

The decision was controversial because the firm had only completed phase I, the results of which were published in The Lancet and phase II, so the announcement implied that it had skipped phase III.

In addition, Reuters noted that the company "had refused to disclose whether inoculation of the vaccine candidate [to the military] was mandatory or optional, citing trade secrets," in an email sent to this news agency.

Regarding this decision, Mercedes Jiménez stresses that "planning a large-scale vaccination before studying the effects on a sufficient number of volunteers [thousands], which is what is required in phase III, is risky ."

For his part, CanSino Biologics President Yu Xuefeng said in a statement that phase I and II clinical trials of the vaccine candidate had shown a " good safety profile and high levels of immune response ." But he cautioned that "trials only show that the vaccine has the potential to prevent COVID-19 and that its authorization to be tested in the military does not guarantee that it will be approved for wider commercial use in the future."

Ad5-nCoV, which is based on a cold adenovirus, is one of eight Chinese candidate vaccines approved for human trials in the country and in others, such as Canada, for the disease caused by the coronavirus.

China has several running candidates. / NOEL CELIS / AFP

4. Sinopharm China

Phase III trials

Chinese public company Sinopharm announced in June that it was going to move to phase III testing of its inactivated virus- based vaccine prototype COVID-19 , which has been developed by one of its subsidiaries: China National Biotec Group ( CNBG), in collaboration with the Wuhan Institutes of Biological Products and Virology.

So far, more than 2,000 people have participated in the tests , which Sinopharm says show that the vaccine would be "safe and effective" and that the adverse reactions were much less than those of other candidates.

Phase III trials will be carried out in the United Arab Emirates, following an agreement to start testing the efficacy of this vaccine in the Gulf state.

The candidate, developed in Wuhan, is one of two inactive vaccines that the CNBG is working on. Another developed by her Beijing institute entered human testing in late April.

The company has built in record time two new vaccine production facilities in Beijing and Wuhan , where CNBG plans to produce 200 million doses of inactivated COVID-19 vaccines a year, according to the state news agency Xinhua.

5. Sinovac Biotech China

Phase III trials

The Chinese private company Sinovac Biotech announced that it is going to start phase III of its inactivated virus vaccine, called CoronaVac. The candidate will be tested at 12 research centers in six Brazilian states with some 9,000 volunteers. This Latin American country has the worst records of cases and deaths from COVID-19, behind only the United States.

The firm noted in June that in phases I and II of its prototype, 90% of the 743 volunteers showed an immune response to the virus and there were no notable adverse effects.

In addition, he reported that he is building a facility to manufacture up to 100 million doses per year.

The Chinese Coronavac will be tested in Brazil.

6. Institute of Medical Biology of China

China phase II trials

The inactivated coronavirus vaccine developed by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (MBCAMS) has entered phase II of clinical trials, Xinhua reports.

There is not much information on this prototype vaccine. The trials will determine the dose of the vaccine and continue to assess whether it has the potential to safely trigger immune responses in healthy people.

IMBCAMS says it hopes to use a dedicated vaccine production plant this year to prepare for China's future vaccine supplies.

7. Imperial College London

United Kingdom, Phase I and II trials

Researchers at Imperial College London developed a 'self-powered' RNA vaccine, which enhances the production of a viral protein to stimulate the immune system.

Phase I and II trials started a few weeks ago with 300 healthy people . The British institution partnered with investment firm Morningside Ventures to manufacture and distribute the vaccine through a new company called VacEquity Global Health.

"We were able to produce a vaccine from scratch and take it to human tests in just a few months," said Robin Shattock, professor of infection and immunity at the institution's medical school, in statements to the BBC.

"If our approach works and the vaccine provides effective protection against disease, it could revolutionize the way we respond to disease outbreaks in the future," he said.

8. BioNTech / Pfizer / Fosun Pharma

Germany, USA, phase I and II trials

German company BioNTech has teamed up with New York-based Pfizer and Chinese drug maker Fosun Pharma to develop its vaccine based on messenger RNA technology. She is the candidate to be tested in Argentina from August; only the approval of the National Administration of Medicines, Food and Medical Technology (ANMAT) remains.

A few days ago, the partners announced promising preliminary results from a phase I and II trial of their mRNA vaccine with 45 healthy volunteers, the data of which has been published in a preprint study. The companies note that the vaccine produced antibodies against SARS-CoV-2 in volunteers , while some experienced moderate side effects such as sleep disturbances and arm pain. 

The project of these companies has the financial support of Operation Warp Speed.

9. INOVIO

United States, phase I trials

The American INOVIO began phase I of clinical trials of its candidate for DNA vaccine against COVID-19, called INO-4800, in April and indicated that it expected to enter phases II and III at the end of the boreal summer.

In phase I, the immune profile of INO-4800 administered by intradermal injection followed by electroporation was evaluated using the company's CELLECTRA 2000 device.

The company released a report on June 30 saying it had achieved preliminary "positive results" in that phase, but the data has not yet been published in a peer-reviewed study.

According to STAT, INOVIO, which has earned more than 4,000 million dollars in its market value (about 3,500 million euros) since the pandemic began, did not provide the necessary details to determine if its vaccine works.

In a press release, the company said its vaccine led to "immune response rates" in 34 of the 36 patients in the small trial, but did not disclose how many produced antibodies that neutralized the coronavirus, key data in determining whether the vaccine could protect against infection.

His project is one of those that have the financial backing of Operation Warp Speed ​​and also has the support of the Bill and Melinda Gates Foundation.

Germany's CureVac began human studies in June. / REUTERS / Kai Pfaffenbach /

10. CureVac Germany

Phase I trials

Germany's CureVac gained media prominence in March when the Donald Trump Administration tried to get the firm to move its investigations to the United States.

To protect CureVac from "suspicious foreign investment and provide financial security without influencing business decisions," the German state has just acquired a 23% stake in the company for a total of 300 million euros, reports Bloomberg.

Furthermore, the firm has just obtained a loan of 75 million euros from the European Investment Bank to boost its manufacturing capacity.

In June, the company, which launched phase I trials of its mRNA vaccine, said its German facility can produce hundreds of millions of doses of vaccines a year .

On the other hand, controversial Tesla CEO Elon Musk recently said on Twitter that his firm is building mobile molecule printers to help make the CureVac vaccine.

The Tübingen-based company also has the support of the Bill and Melinda Gates Foundation. CureVac is a pioneer in the messenger RNA approach, which is also used by BioNTech and its partner Pfizer, as well as Moderna.

Results presented in press releases

Since the coronavirus pandemic began, data from clinical trials came in droppers, usually through press releases, rather than peer-reviewed studies in scientific journals.

Moderna, considered, along with the University of Oxford / Astra Zeneca, as the world leader in this race, was criticized by experts for issuing a press release describing its vaccine in qualitative terms instead of providing concrete data.

So far, the only study published in a peer-reviewed journal was the phase I study by CanSino Biologics and the Chinese Academy of Military Sciences, which published The Lancet.

The emergency situation we are experiencing caused many scientific protocols that have been followed so far to have been blown up. One of the most relevant examples was the scandal of the study of hydroxychloroquine in The Lancet. It remains to be seen how this pandemic will affect the way of doing science and of communicating it in the future.

* Ana Hernando / AgenciaSinc.es

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